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Hypoglycaemic agents These slides should be used in conjunction with the accompanying notes. Options for local implementation NPC. Key therapeutic topics 2010/11 – Medicines management options for local implementation. Second update July 2011.
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Hypoglycaemic agentsThese slides should be used in conjunction with the accompanying notes
Options for local implementationNPC. Key therapeutic topics 2010/11 – Medicines management options for local implementation. Second update July 2011 • In type 2 diabetes mellitus consider carefully the risks and benefits of both intensive glycaemic control and use of hypoglycaemic agents • Review and, where appropriate, revise prescribing to ensure that it is in line with NICE guidance
Key questions • Where does blood glucose control fit within the management of type 2 diabetes? • What is optimal blood glucose control? • What are the preferred hypoglycaemic drugs recommended by NICE? • What is the role of the newer hypoglycaemic drugs? • How are we doing with prescribing?
Type 2 diabetes management is multifactorial Smoking Control blood pressure Education Lifestyle Control blood glucose Individualised care of patients: based on evidence for each intervention Statin Aspirin Metformin These slides should be used in conjunction with the accompanying notes
What is optimal blood glucose control? • Controlling blood glucose requires a careful balance • reducing HbA1c to around 7.5% (59mmol/mol) seems optimal ‘Blood glucose control is an important piece of the jigsaw. There are no arguments in favour of poor glucose control…However, blood glucose control appears to be less effective in reducing cardiovascular disease than controlling either blood pressure or blood lipids.’ MeReC Bulletin Vol. 21 No. 5. Improving outcomes in type 2 diabetes. June 2011
Relationship of reductions in cholesterol, blood pressure and HbA1c with improvements in CHD and CV outcomes Yudkin JS, et al. Diabetologia 2010;53:2079–85, MeReC Bulletin Vol. 21, No. 5, June 2011
What does NICE and QOF say? • Patients should be involved in setting their individualised HbA1c target level, which may be above the general target of 48mmol/mol (6.5%) • Any reduction in HbA1c towards the agreed target is advantageous, but pursuing highly intensive management to HbA1c levels below 48mmol/mol (6.5%) should be avoided NICE Clinical Guideline 87; May 2009 • People with diabetes should agree with their healthcare professional a documented personalised HbA1c target, usually between 48mmol/mol and 58mmol/mol (6.5% and 7.5%), and receive an ongoing review of treatment to minimise hypoglycaemia NICE Quality Standard; March 2011 • QOF awards points for three levels of glucose control • HbA1c of 59mmol/mol (7.5%) or less, 64mmol/mol (8%) or less, and 75mmol/mol (9%) or less
The Goldilocks effectBlood glucose lowering: not too little, not too muchCurrie CJ, et al. Lancet 2010;375:481–9, MeReC Rapid Review No. 1017 Observational study: HbA1c of about 7.5% associated with lowest risk of all-cause mortality (increase above or decrease below this associated with greater risk) Adjusted hazard ratios for all-cause mortality by HbA1c deciles in people given metformin plus sulphonylurea (A) and insulin-based therapy (B) Metformin plus sulphonylurea Insulin-based therapy Vertical error bars show 95%CIs, horizontal bars show HbA1c range. Red circle = reference decile. *Truncated at lower quartile. †Truncated at upper quartile
What does the evidence say about intensifying blood glucose control?MeReC Bulletin Vol. 21, No. 5, June 2011
What are the preferred hypoglycaemic drugs recommended by NICE? What is the role of the newer hypoglycaemic drugs?
Metformin, a sulfonylurea and human NPH (isophane) insulin are the preferred hypoglycaemic drugs recommended by NICE • Newer hypoglycaemic drugs are all usually third-line options • progression to triple therapy should not be automatic
Preferred drug treatment for blood glucose control *This summary is intended only as a guide; it is not comprehensive. See accompanying notes, NICE Clinical Guideline 87; May 2009 and/or NICE pathway on managing type 2 diabetes for details add in NPH insulin* metformin plus sulfonylurea* metformin* Third-line HbA1c ≥ 7.5% (59mmol/mol) or other higher level Safety and tolerability issues Polypharmacy Second-line HbA1c ≥ 6.5% (48mmol/mol) or other higher level First-line
How do the newer drugs compare?MeReC Bulletin Vol. 21, No. 5, June 2011 rosiglitazone withdrawn September 2010
Glitazones: summary (1)Based on NICE Clinical Guideline 87; May 2009 • Can be second-line agents as dual therapy with metformin or a sulfonylurea if either is contraindicated/not tolerated, or if significant risk of hypoglycaemia with a sulfonylurea • Can be third-line agents, as triple therapy with metformin or a sulfonylurea, BUT NPHinsulin preferred • Only continue glitazones if beneficial metabolic response • reduction of at least 0.5% in HbA1c in 6 months • Cochrane concluded: no convincing evidence that patient-orientated outcomes positively influenced by glitazones Richter B, et al. Cochrane Review 2006
Glitazones: summary (2)MHRA web page: Glitazones for diabetes, Drug Safety Update Aug 2011 • Rosiglitazone withdrawn across Europe in September 2010 over concerns of excess cardiovascular risks Pioglitazone▼ • contraindicated in heart failure • monitor for signs/symptoms of fluid retention, weight gain or oedema • stop treatment if any deterioration in cardiac status occurs • do not commence/continue in people with higher risk of fracture • EMA warning about small increased risk of bladder cancer • do not use in people with active/history of bladder cancer or uninvestigated haematuria • assess risk factors for bladder cancer before starting treatment (age, smoking, exposure to occupational/chemotherapy agents, previous irradiation of pelvic region) • particular caution in elderly (bladder cancer and heart failure)
Gliptins: summaryBased on NICE Clinical Guideline 87; May 2009 • Sitagliptin▼ or vildagliptin▼ can be second-line agents as dual therapy with metformin or SU if either is CI/not tolerated, or if significant risk of hypoglycaemia with SU • Sitagliptin can be a third-line agent, as triple therapy, BUT NPHinsulin preferred • Saxagliptin▼ not included in NICE guideline • Only continue gliptins if beneficial metabolic response • Reduction of at least 0.5% in HbA1c in 6 months • Cochrane concluded: long term data especially on cardiovascular outcomes and safety are urgently needed before widespread use is adopted Richter B, et al. Cochrane Review 2008 • No long-term safety data or outcome data
GLP-1 mimetics: summaryBased on NICE Clinical Guideline 87; May 2009 andTechnology Appraisal Guidance 203; October 2010 • Exenatide▼ or liraglutide▼ 1.2mg dailycan be third-line agents, as triple therapy (if patient meets specific body weight criteria), BUT insulin preferred • Liraglutide has very limited role in dual therapy • in people who are unable to take metformin or a sulphonylurea AND are unable to take a glitazone AND are unable to take a gliptin • Only continue exenatide or liraglutide if beneficial metabolic response • Reduction of at least1.0% in HbA1c and weight loss of at least 3% of initial body weight at 6 months • No long-term safety data or outcome data from RCTs • exenatide does have observational cardiovascular outcome data Best JH, et al. Diabetes Care 2011 34:90-95
How are we doing with prescribing? http://www.ic.nhs.uk/pubs/prescribingdiabetes0410 COST
Prescribing comparator: Hypoglycaemic drugsNHSBSA QIPP Prescribing Comparators http://www.nhsbsa.nhs.uk/PrescriptionServices/3332.aspx • Number of prescription items for metformin and sulfonylureas as a percentage of the total number of prescription items for all antidiabetic drugs 94% 76%
Key messages • Management of type 2 diabetes requires individualised multifactorial care • Controlling blood glucose requires a careful balance • reducing HbA1c to around 7.5% (59mmol/mol) seems optimal • Metformin, a sulfonylurea and human NPH insulin are the preferred hypoglycaemic drugs recommended by NICE • Newer hypoglycaemic drugs are all usually third-line options • progression to triple therapy should not be automatic • long term safety of newer hypoglycaemic drugs not known • robust evidence that they help patients live longer or healthier lives not available